Naltrexone is an opioid receptor antagonist with FDA approval for treating opioid addiction since 1984. While typical dose for treating opioid addiction with naltrexone is between 50 mg to 150 mg, the use of low dose naltrexone (LDN) with doses ranging from 1.5 mg to 4.5 mg per day has been growing in popularity. The most common use of LDN has been treating autoimmune disorders; consequently, there have been clinical trials investigating the effectiveness of LDN for clinical conditions such as multiple sclerosis, systemic sclerosis, and Crohn’s disease. More recently, exploring the role low dose naltrexone and ultra-low dose naltrexone (microgram dosing of naltrexone) for chronic pain have been described in the literature. It has been proposed that LDN halts inflammatory cascades via glial cell inactivation. In addition, the role of microgram dosing of naltrexone has shown promise as a means to increase analgesia and decrease tolerance to opioid medications. This review evaluates the existing evidence for using LDN for treating pain and its microgram dosing in the potentiation of opioid medication while reducing side effects.